- Email: [email protected]
Serotonin and premenstrual dysphoric disorder
Intrauterine
endoscopic laser surgery for fetal sacrococcygeal teratoma SIR-A
woman of African origin (gravida 4, para referred at 16 weeks’ gestational age because fetal 4) showed a sacral mass. At sonography, a sonography diagnosis of an external sacrococcygeal tumour with a solid and a cystic component was made. There was no fetal hydrops and the amniotic fluid volume was normal. At 20 weeks, the tumour measured 6X4 cm and polyhydramnios developed, with the deepest vertical pool of amniotic fluid measuring 7 cm. With colour-doppler imaging, the main supplying blood vessel of the tumour could be seen 3 mm under the skin surface of the mediosacral region. After discussion with the parents, comparing possible risks and benefits of expectant management versus endoscopic surgery with an attempt to interrupt the blood supply of the tumour, they opted for the latter. The procedure, which has been performed before to coagulate the communicating placental blood vessels in twin-twin transfusion syndrome and acardiac twins, 1,2 was approved by the ethics committee of the hospital. Under sonographic control (figure), a 1-9 mm diameter rigid fetoscope with a field of vision of 60° was introduced (Olympus, Hamburg, Germany) percutaneously into the amniotic cavity through a sheath with 9-8 Charriere under local anaesthesia and maternal analgesia. A 0-4 mm Nd-YAG laser fibre (mediLas 4060 fibertom, Daimler-Benz Aerospace, Germering, Germany) was passed down the side-arm of the cannula. For fetal analgesia, 0-11 mg morphine was given intramuscularly under ultrasound guidance. It was not possible to reach the sacral area of the fetus where the main artery had been seen; however, we identified small vessels below the surface of the tumour which were coagulated with short laser bursts at 30-50 W. We also perforated the wall of the cystic part of the tumour which consequently collapsed. For the next 3 weeks the situation remained stable. Between 23 and 26 weeks, the tumour increased to 10 X 6 cm and polyhydramnios with a deepest vertical pool of 9-5 cm recurred. Within the cystic area of the tumour, a hyperechogenic netlike pattern suggestive of intraluminal bleeding was seen (figure). At cordocentesis, the haemoglobin was 6 g/dL. After intrauterine transfusion of 38 mL donor blood the haemoglobin was 10-3 g/dL. During fetoscopy we exchanged blood-stained amniotic fluid with artificial fluid to see the tumour. Again, it was impossible clearly to identify the skin above the main stem of the supplying artery. We aimed to reduce tumour volume by
32-year-old
was
Figure: Ultrasound of sacrococcygeal teratoma Left: tumour 1 day before second mtrautenne laser surgery with signs of bleeding into the cystic part. Right: endoscopic laser coagulation of tumour (T) areas by means of a fetoscope (F).
470
vessels visible below the surface of the tumour and we drained old blood from the cystic area into the amniotic fluid, then drained 900 mL of amniotic fluid to restore normal volume. After the procedure, the tumour measured 7X4 cm. There was only a moderate increase in tumour size during the remaining pregnancy and no further bleeding occurred. At 37 weeks, a girl weighing 3500 g and with a haemoglobin of 15-2 g/dL was delivered by elective caesarean section and underwent surgical treatment the same day. The tumour measured 11 X 9 cm and histological examination showed a mixed, partly mature and partly immature, teratoma. She had an uneventful neonatal course after surgery and is now healthy and developing normally at 8 months of age. The prenatal diagnosis of sacrococcygeal teratoma is associated with high fetal mortality3 caused by high-output fetal cardiac failure due to a vascular steal by arteriovenous shunts in the tumour and haemorrhage causing anaemia. Open fetal surgery at 24 weeks for sacrococcygeal teratoma in one case resulted in reversion of fetal hydrops after excision of the tumour, but hysterotomy resulted in premature labour and delivery of a nonviable infant.4 Our procedure may have prevented heart failure and hydrops in this case. The introduction of a second trocar to insert an additional instrument to grasp the external tumour may be helpful to interrupt blood flow in the main arterial vessel.
coagulating
*Kurt Hecher, Bernhard-Joachim Hackelöer Department of Prenatal Diagnosis and Therapy, AK Barmbek, 22291 Hamburg, Germany
1
2
3
Ville Y,
Hyett J, Hecher K, Nicolaides K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995; 332: 224-27. Ville Y, Hyett JA, Vandenbussche FPHA, Nicolaides KH. Endoscopic laser coagulation of umbilical cord vessels in twin reversed arterial perfusion sequence. Ultrasound Obstet Gynecol 1994; 4: 396-98. Flake AW. Fetal sacrococcygeal teratoma. Semin Pediatr Surg 1993; 2: 113-20.
4
Langer JC, Harrison MR, Schmidt KG, et al. Fetal hydrops and death from sacrococcygeal teratoma: rationale for fetal surgery. Am J Obstet Gynecol 1989; 160: 1145-50.
Serotonin and premenstrual disorder
dysphoric
SIR-I believe that van Leusden’s (Dec 2, p 1443)’ statement that premenstrual dysphoric disorder (PDD) is not a serotonin deficiency disease is inaccurate and misleading. Evidence is accumulating that abnormal synthesis or release of brain serotonin in raphe neurons is involved in the pathogenesis of premenstrual dysphoria. A common complaint of women with PDD is increased appetite during the late luteal phase of the cycle. Direct measurements of food intake and mood state made throughout the menstrual cycle have shown a substantial premenstrual increase in caloric intake from carbohydraterich foods, associated with abnormal depression scores, decreased work efficiency, and social withdrawal. A similar association of affective and appetite symptoms has been recorded in patients with seasonal affective disorder’ and in carbohydrate-craving obese people. Like PDD, these disorders also recur cyclically. Individuals with these conditions, including PDD, report improvement in their mood after eating carbohydrate. Carbohydrate consumption without protein has been shown to increase serotonin synthesis and release by increasing brain uptake of serotonin’s aminoacid precursor, tryptophan. We have shown (unpublished data) in a placebocontrolled clinical trial that exogenous administration of 1 g tryptophan can effectively improve the anxiety, depression,
scores in women with severe PDD (n=16). overall dysphoric score for tryptophan treatment was 161-9, SE 66, vs 258-8, SE 62-4, for placebo, p<005.) This study was abruptly discontinued because of the alarm issued by the US Food and Drug Administration about the possible association between tryptophan consumption and eosinophilia-myalgia syndrome. We later found3 that d-fenfluramine, a drug that selectively enhances serotoninmediated neurotransmission, can be effective in relieving the depressed mood and excessive food intake and carbohydrate craving of women with PDD. Other serotonin reuptake blockers have been shown to be effective in premenstrual
and irritability
(The
mean
dysphoria.4 The range of responsiveness of the women in our study and others to serotonin agonists was considerable. This finding is probably attributable to the fact that, as van Leusden indicated, women with PDD are not a homogeneous group, and only a subgroup with serotonin neurotransmission impairment respond positively to the treatment. An involvement of peripheral serotonin in premenstrual symptoms has also been proposed, on the basis of observations that platelet serotonin uptakeS and blood serotonin concentrations were depressed in women with PDD during the luteal phase of the cycle. Serotoninergic dysregulation therefore seems involved in the pathogenesis of PDD, especially of those with associated carbohydrate craving. Drugs that increase serotoninergic transmission could be useful in treating premenstrual disorders of mood and appetite. Amnon Brzezinski
nine showed improvement as measured by the Hamilton rating scale for depression and its addendum, three had positive mood responses during both the drug and placebo trials, and five had inconsistent responses to both placebo and drug and were not shown to be helped by drug treatment.
I also stated that "depressed mood, anxiety, affective lability, and decreased interest in activities occurring later in the chain of events cannot be influenced by progesterone but can be partly alleviated in some cases either by the benzodiazepine alprazolam or by a specific serotonin reuptake inhibitor such as fluoxetine, which have entirely different mechanisms of action. We cannot conclude that PDD is a serotonin deficiency disease". Brzezinski’s remark about involvement of peripheral serotonin in premenstrual symptoms on the basis of observations of platelet serotonin uptake should be regarded with caution. Indeed, elsewherez2 he stated-and I agree-that "however, circulating serotonin is not thought to cross the blood-brain barrier and there is no reason to believe a priori that the mechanisms controlling the synthesis of peripheral serotinin with enterochromaffin cells, or its storage within platelets, are at all related to those regulating its production in and release from brain neurons.". Whereas there is a role for the benzodiazepine alprazolam as well as for fluoxetine (and other serotonin reuptake inhibitors) in PDD, it cannot be concluded that PDD is a serotonin deficiency disease. H A I M van Leusden Benedendorpsweg 90, 6862
WK Oosterbeek, Netherlands
Department of Obstetrics and Gynaecology, Hadassah Medical Centre, Jerusalem, 91120 Israel
1
Leusden HAIM. Premenstrual syndrome no progesterone; disorder no serotonin deficiency. Lancet 1995; 346: 1443-44. Brzezinski A, Wurtman JJ, Wurtman RJ, Gleason R, Greenfield J, Nader T. d-fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstet Gynecol 1990; 76: 296-304. van
premenstrual dysphoric 1 van Leusden HAIM. Premenstrual
premenstrual dysphoric disorder no 2
3
4 5
syndrome no progesterone; serotonin deficiency. Lancet 1995;
346: 1433-44. O’Rourke D, Wurtman JJ, Wurtman RJ, Chebli R, Gleason R. Responses of patients with seasonal affective disorder to dfenfluramine J Clin Pschiatry 1989; 50: 343-47. Brzezinski A, Wurtman JJ, Wurtman RJ, Gleason R, Greenfield J, Nadar T. d-fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstet Gynecol 1990; 76: 296-304. Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. N Engl J Med 1995; 332: 1529-34. Rojansky N, Halbriech U, Zander K, Barkai A, Doldstein S. Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes. Gynecol Obstet Invest 1991; 31: 146-52.
Author’s
reply
SIR-Our views
are not
contradictory,
I believe. I
pointed
out’ that to decide the causation of PDD from treatment
responses has its limitations: drugs may act through a mechanism independent of the one responsible for PDD. The data not justify the claim of a deficiency of a particular substance (eg, progesterone or serotonin). In fact, Brzezinski2 also speaks of the hypothesis that serotonin is
involved. As I said, "the results of the fluoxetine study indicate that, within the non-homogeneous group with PDD, there is a subgroup showing improvement with this serotonin reuptake inhibitor. Here again it is clear that these positive results and the considerable percentage of patients with PDD who do not respond to fluoxetine do not accord with a causal relation between serotonin and PDD". In fact Brzezinski’s’ data also concern such a selected subgroup: eligible patients had to indicate substantial changes in mood and appetite. This is a subgroup of PDD with craving in addition to depressive mood. Even within this subgroup there were differences. In all 17 patients calorie intake was reduced, but
2
Reversible
ageusia associated with losartan
SiR-Hypotension, renal impairment, hyperkalaemia, and cough are well-known adverse effects of angiotensinconverting enzyme (ACE) inhibitors. Less frequent adverse effects are angio-oedema or ageusia.’ Losartan, a selective antagonist of the angiotensin-receptor subtype 1 (AT 1)’ inhibits angiotensin-II-mediated effects and induces haemodynamic changes similar to ACE inhibitors.2 Some adverse effects of ACE inhibitors (eg, cough) which have been linked
the involvement of ACE in kinin metabolism less frequently with AT1-antagonists. We a report patient in whom oral losartan induced progressive taste disturbance with complete but reversible ageusia. A 67-year-old man with a 3-year history of uncomplicated arterial essential hypertension was treated with hydrochlorothiazide/amiloride (25/2-5 mg once daily). No other clinical abnormalities were present and the past medical history was unremarkable. Because of unsatisfactory antihypertensive effect of the diuretics, therapy was changed to losartan (25 mg once daily) with normalisation of blood pressure over the following weeks. About 3 weeks after initiation of therapy, the patient complained of slowly seem
to
to
occur
He described the nature of the taste disturbance as similar to having burnt his mouth, affecting all four primary sensations of taste-sweet, sour, salty, and bitter. After 7 weeks of therapy the patient had complete ageusia and 1 week later he decided to discontinue losartan. Within 2-3 weeks taste returned to normal. Throughout the observation period the patient took no other medications,
progressive dysgeusia.
471
endoscopic laser surgery for fetal sacrococcygeal teratoma SIR-A
woman of African origin (gravida 4, para referred at 16 weeks’ gestational age because fetal 4) showed a sacral mass. At sonography, a sonography diagnosis of an external sacrococcygeal tumour with a solid and a cystic component was made. There was no fetal hydrops and the amniotic fluid volume was normal. At 20 weeks, the tumour measured 6X4 cm and polyhydramnios developed, with the deepest vertical pool of amniotic fluid measuring 7 cm. With colour-doppler imaging, the main supplying blood vessel of the tumour could be seen 3 mm under the skin surface of the mediosacral region. After discussion with the parents, comparing possible risks and benefits of expectant management versus endoscopic surgery with an attempt to interrupt the blood supply of the tumour, they opted for the latter. The procedure, which has been performed before to coagulate the communicating placental blood vessels in twin-twin transfusion syndrome and acardiac twins, 1,2 was approved by the ethics committee of the hospital. Under sonographic control (figure), a 1-9 mm diameter rigid fetoscope with a field of vision of 60° was introduced (Olympus, Hamburg, Germany) percutaneously into the amniotic cavity through a sheath with 9-8 Charriere under local anaesthesia and maternal analgesia. A 0-4 mm Nd-YAG laser fibre (mediLas 4060 fibertom, Daimler-Benz Aerospace, Germering, Germany) was passed down the side-arm of the cannula. For fetal analgesia, 0-11 mg morphine was given intramuscularly under ultrasound guidance. It was not possible to reach the sacral area of the fetus where the main artery had been seen; however, we identified small vessels below the surface of the tumour which were coagulated with short laser bursts at 30-50 W. We also perforated the wall of the cystic part of the tumour which consequently collapsed. For the next 3 weeks the situation remained stable. Between 23 and 26 weeks, the tumour increased to 10 X 6 cm and polyhydramnios with a deepest vertical pool of 9-5 cm recurred. Within the cystic area of the tumour, a hyperechogenic netlike pattern suggestive of intraluminal bleeding was seen (figure). At cordocentesis, the haemoglobin was 6 g/dL. After intrauterine transfusion of 38 mL donor blood the haemoglobin was 10-3 g/dL. During fetoscopy we exchanged blood-stained amniotic fluid with artificial fluid to see the tumour. Again, it was impossible clearly to identify the skin above the main stem of the supplying artery. We aimed to reduce tumour volume by
32-year-old
was
Figure: Ultrasound of sacrococcygeal teratoma Left: tumour 1 day before second mtrautenne laser surgery with signs of bleeding into the cystic part. Right: endoscopic laser coagulation of tumour (T) areas by means of a fetoscope (F).
470
vessels visible below the surface of the tumour and we drained old blood from the cystic area into the amniotic fluid, then drained 900 mL of amniotic fluid to restore normal volume. After the procedure, the tumour measured 7X4 cm. There was only a moderate increase in tumour size during the remaining pregnancy and no further bleeding occurred. At 37 weeks, a girl weighing 3500 g and with a haemoglobin of 15-2 g/dL was delivered by elective caesarean section and underwent surgical treatment the same day. The tumour measured 11 X 9 cm and histological examination showed a mixed, partly mature and partly immature, teratoma. She had an uneventful neonatal course after surgery and is now healthy and developing normally at 8 months of age. The prenatal diagnosis of sacrococcygeal teratoma is associated with high fetal mortality3 caused by high-output fetal cardiac failure due to a vascular steal by arteriovenous shunts in the tumour and haemorrhage causing anaemia. Open fetal surgery at 24 weeks for sacrococcygeal teratoma in one case resulted in reversion of fetal hydrops after excision of the tumour, but hysterotomy resulted in premature labour and delivery of a nonviable infant.4 Our procedure may have prevented heart failure and hydrops in this case. The introduction of a second trocar to insert an additional instrument to grasp the external tumour may be helpful to interrupt blood flow in the main arterial vessel.
coagulating
*Kurt Hecher, Bernhard-Joachim Hackelöer Department of Prenatal Diagnosis and Therapy, AK Barmbek, 22291 Hamburg, Germany
1
2
3
Ville Y,
Hyett J, Hecher K, Nicolaides K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995; 332: 224-27. Ville Y, Hyett JA, Vandenbussche FPHA, Nicolaides KH. Endoscopic laser coagulation of umbilical cord vessels in twin reversed arterial perfusion sequence. Ultrasound Obstet Gynecol 1994; 4: 396-98. Flake AW. Fetal sacrococcygeal teratoma. Semin Pediatr Surg 1993; 2: 113-20.
4
Langer JC, Harrison MR, Schmidt KG, et al. Fetal hydrops and death from sacrococcygeal teratoma: rationale for fetal surgery. Am J Obstet Gynecol 1989; 160: 1145-50.
Serotonin and premenstrual disorder
dysphoric
SIR-I believe that van Leusden’s (Dec 2, p 1443)’ statement that premenstrual dysphoric disorder (PDD) is not a serotonin deficiency disease is inaccurate and misleading. Evidence is accumulating that abnormal synthesis or release of brain serotonin in raphe neurons is involved in the pathogenesis of premenstrual dysphoria. A common complaint of women with PDD is increased appetite during the late luteal phase of the cycle. Direct measurements of food intake and mood state made throughout the menstrual cycle have shown a substantial premenstrual increase in caloric intake from carbohydraterich foods, associated with abnormal depression scores, decreased work efficiency, and social withdrawal. A similar association of affective and appetite symptoms has been recorded in patients with seasonal affective disorder’ and in carbohydrate-craving obese people. Like PDD, these disorders also recur cyclically. Individuals with these conditions, including PDD, report improvement in their mood after eating carbohydrate. Carbohydrate consumption without protein has been shown to increase serotonin synthesis and release by increasing brain uptake of serotonin’s aminoacid precursor, tryptophan. We have shown (unpublished data) in a placebocontrolled clinical trial that exogenous administration of 1 g tryptophan can effectively improve the anxiety, depression,
scores in women with severe PDD (n=16). overall dysphoric score for tryptophan treatment was 161-9, SE 66, vs 258-8, SE 62-4, for placebo, p<005.) This study was abruptly discontinued because of the alarm issued by the US Food and Drug Administration about the possible association between tryptophan consumption and eosinophilia-myalgia syndrome. We later found3 that d-fenfluramine, a drug that selectively enhances serotoninmediated neurotransmission, can be effective in relieving the depressed mood and excessive food intake and carbohydrate craving of women with PDD. Other serotonin reuptake blockers have been shown to be effective in premenstrual
and irritability
(The
mean
dysphoria.4 The range of responsiveness of the women in our study and others to serotonin agonists was considerable. This finding is probably attributable to the fact that, as van Leusden indicated, women with PDD are not a homogeneous group, and only a subgroup with serotonin neurotransmission impairment respond positively to the treatment. An involvement of peripheral serotonin in premenstrual symptoms has also been proposed, on the basis of observations that platelet serotonin uptakeS and blood serotonin concentrations were depressed in women with PDD during the luteal phase of the cycle. Serotoninergic dysregulation therefore seems involved in the pathogenesis of PDD, especially of those with associated carbohydrate craving. Drugs that increase serotoninergic transmission could be useful in treating premenstrual disorders of mood and appetite. Amnon Brzezinski
nine showed improvement as measured by the Hamilton rating scale for depression and its addendum, three had positive mood responses during both the drug and placebo trials, and five had inconsistent responses to both placebo and drug and were not shown to be helped by drug treatment.
I also stated that "depressed mood, anxiety, affective lability, and decreased interest in activities occurring later in the chain of events cannot be influenced by progesterone but can be partly alleviated in some cases either by the benzodiazepine alprazolam or by a specific serotonin reuptake inhibitor such as fluoxetine, which have entirely different mechanisms of action. We cannot conclude that PDD is a serotonin deficiency disease". Brzezinski’s remark about involvement of peripheral serotonin in premenstrual symptoms on the basis of observations of platelet serotonin uptake should be regarded with caution. Indeed, elsewherez2 he stated-and I agree-that "however, circulating serotonin is not thought to cross the blood-brain barrier and there is no reason to believe a priori that the mechanisms controlling the synthesis of peripheral serotinin with enterochromaffin cells, or its storage within platelets, are at all related to those regulating its production in and release from brain neurons.". Whereas there is a role for the benzodiazepine alprazolam as well as for fluoxetine (and other serotonin reuptake inhibitors) in PDD, it cannot be concluded that PDD is a serotonin deficiency disease. H A I M van Leusden Benedendorpsweg 90, 6862
WK Oosterbeek, Netherlands
Department of Obstetrics and Gynaecology, Hadassah Medical Centre, Jerusalem, 91120 Israel
1
Leusden HAIM. Premenstrual syndrome no progesterone; disorder no serotonin deficiency. Lancet 1995; 346: 1443-44. Brzezinski A, Wurtman JJ, Wurtman RJ, Gleason R, Greenfield J, Nader T. d-fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstet Gynecol 1990; 76: 296-304. van
premenstrual dysphoric 1 van Leusden HAIM. Premenstrual
premenstrual dysphoric disorder no 2
3
4 5
syndrome no progesterone; serotonin deficiency. Lancet 1995;
346: 1433-44. O’Rourke D, Wurtman JJ, Wurtman RJ, Chebli R, Gleason R. Responses of patients with seasonal affective disorder to dfenfluramine J Clin Pschiatry 1989; 50: 343-47. Brzezinski A, Wurtman JJ, Wurtman RJ, Gleason R, Greenfield J, Nadar T. d-fenfluramine suppresses the increased calorie and carbohydrate intakes and improves the mood of women with premenstrual depression. Obstet Gynecol 1990; 76: 296-304. Steiner M, Steinberg S, Stewart D, et al. Fluoxetine in the treatment of premenstrual dysphoria. N Engl J Med 1995; 332: 1529-34. Rojansky N, Halbriech U, Zander K, Barkai A, Doldstein S. Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes. Gynecol Obstet Invest 1991; 31: 146-52.
Author’s
reply
SIR-Our views
are not
contradictory,
I believe. I
pointed
out’ that to decide the causation of PDD from treatment
responses has its limitations: drugs may act through a mechanism independent of the one responsible for PDD. The data not justify the claim of a deficiency of a particular substance (eg, progesterone or serotonin). In fact, Brzezinski2 also speaks of the hypothesis that serotonin is
involved. As I said, "the results of the fluoxetine study indicate that, within the non-homogeneous group with PDD, there is a subgroup showing improvement with this serotonin reuptake inhibitor. Here again it is clear that these positive results and the considerable percentage of patients with PDD who do not respond to fluoxetine do not accord with a causal relation between serotonin and PDD". In fact Brzezinski’s’ data also concern such a selected subgroup: eligible patients had to indicate substantial changes in mood and appetite. This is a subgroup of PDD with craving in addition to depressive mood. Even within this subgroup there were differences. In all 17 patients calorie intake was reduced, but
2
Reversible
ageusia associated with losartan
SiR-Hypotension, renal impairment, hyperkalaemia, and cough are well-known adverse effects of angiotensinconverting enzyme (ACE) inhibitors. Less frequent adverse effects are angio-oedema or ageusia.’ Losartan, a selective antagonist of the angiotensin-receptor subtype 1 (AT 1)’ inhibits angiotensin-II-mediated effects and induces haemodynamic changes similar to ACE inhibitors.2 Some adverse effects of ACE inhibitors (eg, cough) which have been linked
the involvement of ACE in kinin metabolism less frequently with AT1-antagonists. We a report patient in whom oral losartan induced progressive taste disturbance with complete but reversible ageusia. A 67-year-old man with a 3-year history of uncomplicated arterial essential hypertension was treated with hydrochlorothiazide/amiloride (25/2-5 mg once daily). No other clinical abnormalities were present and the past medical history was unremarkable. Because of unsatisfactory antihypertensive effect of the diuretics, therapy was changed to losartan (25 mg once daily) with normalisation of blood pressure over the following weeks. About 3 weeks after initiation of therapy, the patient complained of slowly seem
to
to
occur
He described the nature of the taste disturbance as similar to having burnt his mouth, affecting all four primary sensations of taste-sweet, sour, salty, and bitter. After 7 weeks of therapy the patient had complete ageusia and 1 week later he decided to discontinue losartan. Within 2-3 weeks taste returned to normal. Throughout the observation period the patient took no other medications,
progressive dysgeusia.
471